The focus of this project is the use of MRI to understand the pathophysiology of multiple sclerosis (MS) and to determine whether disease activity is altered by various immunomodulatory treatments such as Anti-Tac antibodies or Roliprom, a phosphodiesterase 4 inhibitor and to monitor the natural history of MS. Magnetization Transfer (MT) imaging which is sensitive to the amount of bound and free water in the white matter and indirectly reflects myelination was also used to evaluate these patients. MT region of interest (ROI) analysis of individual enhancing or non-enhancing lesions reveals that there is no difference in the pattern of MS lesion recovery either when a lesion develops during the natural history of the disease or receiving INFB-1b. However, there does appear to be a faster improvement in the MTR recovery towards baseline when enhancing lesions occur in association with a clinical exacerbation requiring treatment with intravenous steroids. These results would indicate that closure of the blood brain barrier with steroids is associated with a decrease in the ratio of free to bound water within a MS lesion that is detected as a change in MTR. MTR studies performed of MS lesions in patients receiving rhIGF-1 suggest that a similar recovery pattern as observed with steroids which would be consistent with the proposed anti-inflammatory effects of this agent. In 2000, the open-labeled baseline versus treatment trial is evaluating Altered Peptide Ligand (APL) as a treatment for relapsing-remitting MS patients closed due to significant server adverse events. APL is thought to interfere with binding of T-cell to antigen presenting cells and induce tolerance in the MS patients. APL appeared to alter the T-cells to pro-inflammatory phenotype thus possibly stimulating MS disease progression as documented on MRI. Further immunologic-imaging evaluations of the patients with unresponsive MS to conventional therapy is ongoing using Anti-Tac antibodies directed against T-cells and in 5 patients the combination of interferon and Anti-Tac antibodies is well tolerated with a decrease in enhancing lesions. A phase II trial is underway evaluating the new oral agent, Roliprom for the treatment of relapsing remitting MS patients using suppression of frequency of enhancing lesions as an outcome measure.